Experimental allergic encephalomyelitis (EAE) is induced in guinea pigs by injection of either purified myelin basic protein or whole CNS tissue in complete Freund's adjuvant (CFA). Disease can be prevented or reversed by injection of the animals with myelin basic protein in incomplete Freund's adjuvant (IFA). By using purified peptides derived from BP, we have found that only molecular containing the encephalitogenic site are capable of affording complete protection against EAE. While the immune mechanism of disease prevention is unknown, our data indicate that disease reversal must be mediated at least partially by antigen interaction with sensitized cells. Although we have found no evidence of suppressor T cells, they could be involved in disease prevention.